Alzheimer Related News Items

News as of 7/07/03

For more info on these abstracts write/call Ed Cabic (edcabic@comcast.net or 410-992-7197)

NOTE - e-mail address change to new address as of 2/02

For more AD information, see Alzheimer Information athttp://www.connext.net/~seniors/infoad.htm

Copies of these reports are posted there

This web page was started at the Florence Bain Senior Center in Columbia MD

Drugs

Desperate Families Embrace Unapproved AD Drug - NY Times reporter Gina Kolata tells of individuals who are taking an AD drug Memantine. The drug blocks a brain chemical, glutamate, which has been implicated in nerve cell death. A new study found that it seemed to have a modest effect in alleviating the symptoms of advanced AD. For now, it is not sold in this country. Forest Laboratories, which has licensed it, has applied to the Food and Drug Administration to market it and does not expect to hear anything until fall. The drug is sold in Europe, and the F.D.A. generally allows patients to import unapproved drugs for their personal use if there is no approved treatment for their condition and if they can supply the name and address of a doctor who will supervise the treatment. And there are plenty of Internet companies ready to fill the demand. GlobalRx, which has just four full-time employees, says it had 150 memantine clients a few months ago. Now, with about 600, it says it cannot handle any more orders. A British company, International Antiaging Systems, which will ship the drug even without a doctor’s order, says it is supplying about 500 patients most of whom are in the United States. The families pay for memantine out of pocket, typically $150 to $175 a month, plus about $60 for express delivery. The phenomenon has taken AD experts by surprise. Doctors are agonizing over what to do. As researchers, they respect the F.D.A.’s strict demands that drugs be shown to be both safe and efficacious before they are approved. They also know too well that some drugs that seemed promising emerged as useless, or even dangerous, when subjected to the agency’s scrutiny. Yet they see the anguish of family members who are desperate for something to slow the progress of the degenerative brain disease. “We are all conflicted about this,” said Dr. Ronald Petersen, director of the Mayo Clinics AD Research Center in Rochester, Minn. “We want to help our patients and not endanger them, and at the same time we have a moral and ethical obligation to follow the F.D.A.’s guideline.” By Gina Kolata NY Times 6/15/03

AD Drug Disappoints - Forest Labs - Forest Laboratories Inc. said on 6/19/03 a clinical trial of an experimental treatment involving their Memantine and Pfizer’s Aricept did not significantly improve awareness and reasoning in patients with mild to moderate AD. The trial results, which could slash the potential market for the drug, sent Forest shares down more than 11 percent. Forest late last year submitted an application to market the drug for moderate to severe AD, based on successful trial results in those patients. The company said on 6/19/03 it did not believe the application would be affected by the recent trial results testing cognition -- awareness of surroundings and ability to take in information -- among mild-to-moderate patients. Forest said it still hoped to have the drug on the U.S. market by the middle of next year. However, if only moderate-to-severe patients are administered the drug, it would severely dent Forest’s potential market, analysts said. Forest noted the distinction between the patient populations. “It may be harder to demonstrate the efficacy of combination therapy in patients with milder forms of AD when they are already being treated with an effective agent,” Dr. Lawrence Olanoff, executive vice president of Forest, said in a statement. By Jed Seltzer Reuters 6/19/03

Genes & Genetic Issues

AMA: No Ethical Barriers to Cloning for Research - The American Medical Association on 6/17/03 gave its ethical go-ahead to cloning embryos for medical research, but not for its use to produce babies. Dr. Michael S. Goldrich, chair-elect of the AMA’s Council on Ethical and Judicial Affairs (CEJA), said at a press conference that the action allows physicians to ethically pursue the “science of therapeutic cloning.” This science involves creating early embryos in order to harvest their stem cells, so-called master cells capable of maturing into any type of tissue in the body. Researchers hope stem cells can eventually be used to replace the damaged tissue that marks a host of ills, including AD, diabetes and heart disease. By Peggy Peck Reuters Health 6/17/03

AD Gene Ups Seizure Risk After Brain Injury - People who experience serious brain injuries are at risk of developing seizures as a result, and new research suggests that the risk may be higher among people who also carry a form of a gene linked to AD. Investigators at the University of Texas Southwestern Medical Center in Dallas discovered that, among people with brain injuries, those who carried the e4 version of a gene called apolipoprotein E (APOE) were more than twice as likely to develop seizures six months after their injuries. This form of the APOE gene has been associated with an increased risk of AD. Currently, no treatment prevents seizures before they start, and further research into the role of APOE in causing epilepsy among brain-injured people may lead to new drugs that fight the condition. Of several different versions of the APOE gene, the e4 form has been linked to AD. People with one or two copies of APOE-e4 (from one or both parents) are at greater risk than those with a different combination of APOE genes. This is not the first study to uncover a link between APOE-e4 and recovery after brain injury, and previous research has found that e4 carriers had more impaired memory following brain injury than other brain-injured people. Reuters Health 6/17/03 Archives of Neurology 2003;60:818-822

In AD, Plaques May Alter Memory Genes - The buildup of toxic proteins in the brains of AD patients is accompanied by changes in several genes linked to memory and learning, a new study has found. The study, which looked at both mice and humans, found that brain cell genes known to regulate memory and learning were significantly suppressed in the presence of plaques composed of a renegade protein called beta-amyloid. The collective evidence strongly suggests that the start of amyloid deposits in the brain selectively reduces expression of a group of genes highly sensitive to amyloid and essential for forming new memories. Many AD researchers believe these plaques cause the dementia and other mental decline that mark the condition. Dave Morgan, an AD expert at the University of South Florida in Tampa, and the leader of the study, says the work could open a new frontier in the search for therapies to fight the disease. So far, scientists have come at AD from three directions: (1) drugs that block the buildup of protein deposits, (2) “plaque-busting” drugs that break up the protein clusters and allow the brain to clear them away and (3) vaccines that encourage the immune system to destroy the plaques. The fourth way, Morgan says, would be to use the latest information and subsequent research to design drugs that could reverse the effects of beta-amyloid on brain genes. “I don’t know that these drugs would ever be useful by themselves,” he says, but they could augment some or all of the other treatments. No such compounds are in development yet, Morgan adds. By Adam Marcus HealthDay Reporter (HealthDay is the new name for HealthScoutNews.) 6/26/03 Journal of Neuroscience. June 15, 2003, 23(12)5219-5226

Caregivers

Tube Feeding Rates Vary by Nursing Home - Roughly one-third of nursing home residents who are in an advanced stage of dementia are given feeding tubes, according to a study out 7/1/03. In the final stages of AD, patients often lose the ability to eat and swallow. While feeding tubes can deliver fluid and nutrients directly to a patient’s stomach, experts say they may do more harm than good. The tubes can cause discomfort and have no demonstrable health benefits in such patients, according to the report. The new study suggests that whether a patient is given a feeding tube varies greatly from nursing home to nursing home. A team led by Dr. Susan L. Mitchell, of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, looked at more than 180,000 patients with advanced dementia who were residing in Medicare- or Medicaid-certified nursing homes in the U.S. in 1999. They found that 34 percent of such patients had feeding tubes. Patients were more likely to be given a feeding tube if they were younger, non-white, male or divorced. The use of the tubes was also more likely among those who lacked an advance directive (a document that reflects the patient’s wishes), who had a recent decline of functional status or who lacked a diagnosis of AD. After controlling for these patient factors, the authors found that patients who lived in for-profit nursing homes, homes that were located in urban areas, homes that had more than 100 patients or homes that lacked a special dementia care unit were more likely to get a feeding tube. “This study confirms that feeding tube use among older persons with advanced cognitive impairment varies depending on the characteristics of the nursing home in which they reside,” the authors write. One of the “most notable observations” in the study, the researchers conclude, is the “increased feeding tube use among residents living in for-profit nursing homes.” It takes more time for staff to feed patients by hand, so feeding tube use may be seen as a money-saver by nursing homes -- although this has not been proven, according to the report. Reuters Health 7/1/03 Journal of the American Medical Association 2003;290:73-80

Caregivers Face Getting Sick Themselves - The stress of caring for an AD patient at home can prematurely age the immune system, putting caregivers at risk of developing a raft of age-related diseases, a study reports 7/1/03. This study focused on the health of older caregivers, but the findings also might apply to some of the 20 million caregivers and family members of AD patients. This study suggests caregivers under the most stress run the risk of getting sick themselves with illnesses like heart disease or cancer. “Caregivers are often called the second victims of AD,” says the lead author of the study, Janice Kiecolt-Glaser. She and Ronald Glaser, both at the Ohio State University, knew that caregivers of AD patients often face a job with unrelenting stress. They recruited 119 seniors who were caring for a spouse with AD or another form of dementia, which the Chicago-based AD Association says can require up to 100 hours a week. The researcher compared the caregivers with 106 senior citizens who didn’t have to care for a chronically ill spouse. Throughout the six-year study, the team took blood samples from the recruits and measured the levels of a naturally produced immune chemical called interleukin-6, or IL-6. The team knew IL-6 increased with age and can put people at risk for a host of illnesses. They found that the levels of IL-6 increased four times as fast in the caregivers during the study. Controls also had an increase -- a natural part of aging -- but it was no where near as rapid as that of the caregivers, the team found. Caregivers, who were about 70 at the time of the study, had IL-6 levels that looked like those of the average 90-year-old, Glaser says. African-American caregivers in the study had the highest IL-6 levels. The ill effects of stress may persist: Three years after a spouse had died, all caregivers in the study had IL-6 levels that remained too high. For older caregivers, the threat of a disease like heart disease or cancer is particularly alarming: Another study suggests caregivers of someone with a chronic illness ran a 63% greater risk of dying prematurely -- often of an age-related illness that could have been triggered by stress, Glaser says. By Kathleen Fackelmann USA TODAY 7/1/03 Proceedings of the National Academy of Sciences USA, 10.1073/pnas.1531903100

Arts, Technology May Help Dementia Patients - Artistic pursuits and a hand-held computer could help people suffering from dementia to express themselves and remember appointments and events, British researchers said 6/24/03. At the British Psychological Society meeting at the University of East Anglia in eastern England scientists said patients can express themselves and communicate through art and the latest technology. “We’ve run a number of pilot projects in different art forms and found extraordinary things happening,” said John Killick, of the University of Stirling in Scotland. Patients who had difficulty communicating through speech displayed an amazing ability to express themselves through photography, collage and sculpture. Although it did not improve their cognitive ability, patients conveyed what they were feeling in ways they had never done before. “We need to do far more research and give far more opportunities to people with dementia to express themselves in alternative ways,” Killick added in an interview. Other scientists have turned to technology and adapted a tiny computer called the MemoJog to help patients and their carers remember dates, appointments, when to take medicines or even what day it is. About the size of personal digital assistants (PDAs), the device is easy to program and can improve the quality of life and independence for people with memory problems, Dr Jonathan Evans told the meeting. “Our initial findings suggest that the MemoJog device may be useful for at least some people with memory impairment, including older users. Most of participants reported that it was easy to learn how to use MemoJog and that it was of benefit to them in remembering their day-to-day activities,” he said. By Patricia Reaney Reuters 6/24/03

Prevention

With the Mind in Old Age, It’s Use It or Lose It - Keeping up leisure activities such as reading, playing board games and dancing may help the elderly stay mentally sharp into their later years, researchers at the Albert Einstein College of Medicine in New York said 6/19/03. They found that by following 469 dementia-free people over 75 who engaged in leisure activities they were less likely to show signs of dementia than others. But not all activities appeared equally effective in reducing dementia risk. For instance, people who reported frequently playing board games, reading, playing a musical instrument or doing crossword puzzles were less likely to develop dementia than those who said they engaged in those activities only rarely. However, frequently joining group discussions and writing appeared to offer no protection against memory-robbing diseases like AD. Elderly people who reported often taking a turn on the dance floor were less likely to show signs of dementia, but no other form of physical activity appeared to have any effect on dementia risk, the report indicates. In an interview with Reuters Health, study author Dr. Joe Verghese said that mind-bending activities may stave off dementia by increasing a person’s “cognitive reserve.” For instance, engaging in mental exercise may increase the connections between brain cells or promote new networks between cells, Verghese said. So while people who perform these activities may get dementia as often as others, mentally active people can perhaps afford to lose more brain cells before symptoms appear, he noted. Based on these findings, Verghese said he believed that people who work with the elderly should “definitely” encourage them to take part in mental exercise, similar to the activities featured in the current study. By Alison McCook Reuters Health 6/18/03 The New England Journal of Medicine 2003;348:2508-2516, 2489-2490

Small Study Suggests Insulin-AD Link - New research suggests that high levels of insulin may boost production of brain proteins that are linked to AD. In a small speculative study, investiga-tors found that giving older people very high doses of insulin increased the amount of a starchy protein that forms plaques in the brains of people with AD. The relationship between insulin and levels of the protein was most pronounced in the oldest participants. The results suggest that treatments that lower insulin levels or improve its effectiveness may help delay or prevent AD, Dr. Suzanne Craft of the Veterans Affairs Puget Sound Health Care System in Seattle said in an interview with Reuters Health. The results also underscore the importance of treating and preventing diabetes, making it increasingly clear that “high insulin levels are bad for your brain, as well as for your body,” she told Reuters Health. People with type 2 diabetes often lose their sensitivity to insulin, and have elevated blood levels of the blood-sugar-regulating hormone. Type 2 diabetes, the most common form of the disease, typically develops later in life and is often related to lifestyle and obesity. By Natalie Engler Reuters Health 6/23/03 Neurology 2003;60:1886-1887,1899-1903

Education Helps Ward Off AD, Study Finds - Playing games and solving puzzles may help prevent AD, but getting a good education may help your brain overcome its effects, U.S. researchers said on 6/23/03. Higher learning may help the brain become more elastic -- either giving a person a reserve of brain cells to call on when AD strikes, or perhaps helping the brain re-wire itself to bypass the rotted-out parts, they said. The study of 130 nuns, priests and monks with AD showed large differences in real-world functioning of those who had more education. Each volunteer took a test of cognitive function -- awareness, reasoning and judgment -- about eight months on average before dying. After death, their brains were examined and analyzed. Those who had more education seemed to have been affected less by the plaques -- the characteristic blobs of dead brain cells -- that are a hallmark of AD. Usually, the more plaques a person with AD has, the less well he or she functions. But education offset this effect, Dr. David Bennett of Rush Presbyterian-St. Luke’s Medical Center in Chicago and colleagues there and at the University of Pennsylvania found. Education “may make the brain more adaptable and flexible, similar to what we have seen demonstrated in experimental animals,” Bennett said in a statement. By Maggie Fox, Reuters Health and Science Correspondent 6/23/03 Neurology 2003;60:1909-1915

Other Items

Nicotine Byproduct May Counter AD Plaques - A byproduct of nicotine metabolism may prevent the formation of the brain-clogging plaques linked with AD, according to a test-tube study. The preliminary finding offers a potential explanation for previous research linking cigarette smoking with a delayed onset of AD, said study author Dr. Kim D. Janda, a professor of chemistry at the Scripps Research Institute in La Jolla, California. But this controversial line of investigation is in its infancy, and some researchers have concluded that smoking may promote dementia. People worried about developing AD should certainly not start lighting up in an effort to ward off the mind-robbing disease, Janda told Reuters Health. “I would never tell anyone to smoke,” he said. The researchers reported that nornicotine, a nicotine byproduct, prevented beta-amyloid proteins from clumping together in a test tube to form the plaques found in AD patients. These plaques can kill brain cells, though it is not clear whether they are a cause or consequence of the disease. Janda said the reason for their finding is a process known as glycation, in which nornicotine, sugars and beta-amyloid react together, rendering the proteins unable to bind with each other. Since nornicotine is toxic to cells, it’s unlikely to ever be used therapeutically, he said. But if further research confirms the new study, the hope would be to develop a drug that mimics nornicotines beneficial action without causing its side effects, Janda said. By Jacqueline Stenson Reuters Health 6/16/03 Proceedings of the National Academy of Sciences July 8, 2003;100(14):8182-8187

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